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Opposite Roles of BAP1 in Overall Survival of Uveal Melanoma and Cutaneous Melanoma

Background: BRCA1-Associated Protein 1 (BAP1) germline mutations predispose individuals to cancers, including uveal melanoma (UM) and cutaneous melanoma (CM). BAP1 loss is common in UM and is associated with a worse prognosis. BAP1 loss is rare in CM and the outcome is unclear. Methods: UM and CM da...

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Autores principales: Liu-Smith, Feng, Lu, Yunxia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074098/
https://www.ncbi.nlm.nih.gov/pubmed/32028647
http://dx.doi.org/10.3390/jcm9020411
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author Liu-Smith, Feng
Lu, Yunxia
author_facet Liu-Smith, Feng
Lu, Yunxia
author_sort Liu-Smith, Feng
collection PubMed
description Background: BRCA1-Associated Protein 1 (BAP1) germline mutations predispose individuals to cancers, including uveal melanoma (UM) and cutaneous melanoma (CM). BAP1 loss is common in UM and is associated with a worse prognosis. BAP1 loss is rare in CM and the outcome is unclear. Methods: UM and CM data was retrieved from The Cancer Genome Atlas (TCGA) database. Cox regression model was performed to examine whether BAP1 mRNA levels or copy number variations were associated with overall survival (OS). Results: BAP1-low mRNA predicted a poor OS in UM (HR = 9.57, 95% CI: 2.82, 32.5) but a contrasting better OS in CM (HR = 0.73, 95% CI: 0.56, 0.95). These results remained unchanged after adjusting for sex, age, and stage in UM and CM, or after adjusting for ulceration or Breslow depth in CM. Additionally, low BAP1 mRNA predicted a better OS in CM patients older than 50 years but not in younger patients. Co-expression and enrichment analysis revealed differential genes and mutations that were correlated with BAP1 expression levels in UM and CM tumors. Conclusions: Low BAP1 mRNA was significantly associated with a better OS in CM patients, in sharp contrast to UM. High BAP1 expression in CM was significantly associated with over-expressed CDK1, BCL2, and KIT at the protein level which may explain the poor OS in this sub-group of patients. Function of BAP1 was largely different in CM and UM despite of a small subset of shared co-expressed genes.
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spelling pubmed-70740982020-03-19 Opposite Roles of BAP1 in Overall Survival of Uveal Melanoma and Cutaneous Melanoma Liu-Smith, Feng Lu, Yunxia J Clin Med Article Background: BRCA1-Associated Protein 1 (BAP1) germline mutations predispose individuals to cancers, including uveal melanoma (UM) and cutaneous melanoma (CM). BAP1 loss is common in UM and is associated with a worse prognosis. BAP1 loss is rare in CM and the outcome is unclear. Methods: UM and CM data was retrieved from The Cancer Genome Atlas (TCGA) database. Cox regression model was performed to examine whether BAP1 mRNA levels or copy number variations were associated with overall survival (OS). Results: BAP1-low mRNA predicted a poor OS in UM (HR = 9.57, 95% CI: 2.82, 32.5) but a contrasting better OS in CM (HR = 0.73, 95% CI: 0.56, 0.95). These results remained unchanged after adjusting for sex, age, and stage in UM and CM, or after adjusting for ulceration or Breslow depth in CM. Additionally, low BAP1 mRNA predicted a better OS in CM patients older than 50 years but not in younger patients. Co-expression and enrichment analysis revealed differential genes and mutations that were correlated with BAP1 expression levels in UM and CM tumors. Conclusions: Low BAP1 mRNA was significantly associated with a better OS in CM patients, in sharp contrast to UM. High BAP1 expression in CM was significantly associated with over-expressed CDK1, BCL2, and KIT at the protein level which may explain the poor OS in this sub-group of patients. Function of BAP1 was largely different in CM and UM despite of a small subset of shared co-expressed genes. MDPI 2020-02-03 /pmc/articles/PMC7074098/ /pubmed/32028647 http://dx.doi.org/10.3390/jcm9020411 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liu-Smith, Feng
Lu, Yunxia
Opposite Roles of BAP1 in Overall Survival of Uveal Melanoma and Cutaneous Melanoma
title Opposite Roles of BAP1 in Overall Survival of Uveal Melanoma and Cutaneous Melanoma
title_full Opposite Roles of BAP1 in Overall Survival of Uveal Melanoma and Cutaneous Melanoma
title_fullStr Opposite Roles of BAP1 in Overall Survival of Uveal Melanoma and Cutaneous Melanoma
title_full_unstemmed Opposite Roles of BAP1 in Overall Survival of Uveal Melanoma and Cutaneous Melanoma
title_short Opposite Roles of BAP1 in Overall Survival of Uveal Melanoma and Cutaneous Melanoma
title_sort opposite roles of bap1 in overall survival of uveal melanoma and cutaneous melanoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074098/
https://www.ncbi.nlm.nih.gov/pubmed/32028647
http://dx.doi.org/10.3390/jcm9020411
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